1-181483467-C-T

Position:

• chr1-181483467-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000367570(CACNA1E):​c.-278C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0029 in 320,632 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0041 (4 hom., cov: 31)
  • Exomes 𝑓: 0.0018 (0 hom.)
• Consequence: CACNA1E ENST00000367570 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.805

Genes affected

CACNA1E (HGNC:1392): (calcium voltage-gated channel subunit alpha1 E) Voltage-dependent calcium channels are multisubunit complexes consisting of alpha-1, alpha-2, beta, and delta subunits in a 1:1:1:1 ratio. These channels mediate the entry of calcium ions into excitable cells, and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. This gene encodes the alpha-1E subunit of the R-type calcium channels, which belong to the 'high-voltage activated' group that maybe involved in the modulation of firing patterns of neurons important for information processing. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2011]

CACNA1E (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 1-181483467-C-T is Benign according to our data. Variant chr1-181483467-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1300917.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00413 (628/152152) while in subpopulation AMR AF= 0.00556 (85/15286). AF 95% confidence interval is 0.00508. There are 4 homozygotes in gnomad4. There are 329 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 628 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CACNA1E	NM_001205293.3	c.-278C>T		upstream_gene_variant		ENST00000367573.7	NP_001192222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CACNA1E	ENST00000367570	c.-278C>T		5_prime_UTR_variant	1/47	1		ENSP00000356542.1
CACNA1E	ENST00000524607.6	c.435-277C>T		intron_variant		5		ENSP00000432038.2
CACNA1E	ENST00000533229.1	n.157C>T		non_coding_transcript_exon_variant	1/7	1
CACNA1E	ENST00000367573.7	c.-278C>T		upstream_gene_variant		1	NM_001205293.3	ENSP00000356545.2

Frequencies

GnomAD3 genomes AF: 0.00413 AC: 628 AN: 152034 Hom.: 4 Cov.: 31

Gnomad AFR AF: 0.000822

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00557

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00964

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00554

Gnomad OTH AF: 0.00670

GnomAD4 exome AF: 0.00179 AC: 302 AN: 168480 Hom.: 0 Cov.: 0 AF XY: 0.00185 AC XY: 158 AN XY: 85410

Gnomad4 AFR exome AF: 0.000189

Gnomad4 AMR exome AF: 0.00164

Gnomad4 ASJ exome AF: 0.000148

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00268

Gnomad4 FIN exome AF: 0.00324

Gnomad4 NFE exome AF: 0.00210

Gnomad4 OTH exome AF: 0.00128

GnomAD4 genome AF: 0.00413 AC: 628 AN: 152152 Hom.: 4 Cov.: 31 AF XY: 0.00442 AC XY: 329 AN XY: 74376

Gnomad4 AFR AF: 0.000819

Gnomad4 AMR AF: 0.00556

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00291

Gnomad4 FIN AF: 0.00964

Gnomad4 NFE AF: 0.00554

Gnomad4 OTH AF: 0.00663

Alfa AF: 0.00540 Hom.: 0

Bravo AF: 0.00350

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	17
DANN	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs189902582; hg19: chr1-181452603;